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The modulation of Th2 immune pathway in the immunosuppressive effect of human umbilical cord mesenchymal stem cells in a murine asthmatic model

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Abstract

Background

Asthma is a chronic airway inflammatory disease that has a high prevalence nowadays, and seeking the means of relieving asthmatic symptoms is now an issue with increased importance. While mesenchymal stem cells have been demonstrated to display immunomodulatory effects, the effect of fetus-type mesenchymal stem cells (MSCs) on asthmatic symptoms in vivo have not been reported to date.

Methods

Female BALB/c mice at 8 weeks of age were sensitized by ovalbumin, and MSCs derived from Wharton’s jelly of human umbilical cord mesenchymal stem cells (hUCMSCs) were injected into the asthmatic mice. Airway hyper-responsiveness, lung eosinophil infiltration, cytokine level in splenocyte cultures and serum immunoglobulin level were measured. Enzyme-linked immunosorbent assay was used to determine cytokine and immunoglobulin levels.

Results

This current study demonstrated that hUCMSCs attenuated both lung lymphocyte and eosinophil infiltration, and significantly decreased the concentration of Th2 cytokines interleukin-5 in splenocyte cultures.

Conclusions

Human umbilical cord mesenchymal stem cells have the advantage of being easily harvested non-invasively and are capable of rapid proliferation, therefore an ideal material for stem cell-based immune therapies. The current study showed that fetal-type MSCs were able to suppress asthmatic symptoms efficiently, and its immunomodulatory effect resulted primarily from suppressing the Th2 pathway in the animal model. This study suggested that hUCMSCs could be an ideal candidate for cell-based therapies of asthma.

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References

  1. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Investig. 1999;103:1103–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Deng J, Petersen BE, Steindler DA, Jorgensen ML, Laywell ED. Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells. 2006;24:1054–64.

    Article  CAS  PubMed  Google Scholar 

  3. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2004;103:1669–75.

    Article  CAS  PubMed  Google Scholar 

  4. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  CAS  PubMed  Google Scholar 

  5. Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M, Takimoto R, Iyama S, Matsunaga T, Ohtani S, Matsuura A, Hamada H, Niitsu Y. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 2005;106:756–63.

    Article  CAS  PubMed  Google Scholar 

  6. Abdallah BM, Kassem M. Human mesenchymal stem cells: from basic biology to clinical applications. Gene Ther. 2008;15:109–16.

    Article  CAS  PubMed  Google Scholar 

  7. Jones BJ, McTaggart SJ. Immunosuppression by mesenchymal stromal cells: from culture to clinic. Exp Hematol. 2008;36:733–41.

    Article  CAS  PubMed  Google Scholar 

  8. Lee SM, Lee SC, Kim SJ. Contribution of human adipose tissue-derived stem cells and the secretome to the skin allograft survival in mice. J Surg Res. 2014;188:280–9.

    Article  CAS  PubMed  Google Scholar 

  9. Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol. 2010;299:L760–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fan CG, Zhang QJ, Zhou JR. Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev. 2011;7:195–207.

    Article  PubMed  Google Scholar 

  11. Chan CK, Wu KH, Lee YS, Hwang SM, Lee MS, Liao SK, Cheng EH, See LC, Tsai CN, Kuo ML, Huang JL. The comparison of interleukin 6-associated immunosuppressive effects of human ESCs, fetal-type MSCs, and adult-type MSCs. Transplantation. 2012;94:132–8.

    Article  PubMed  Google Scholar 

  12. Huang YC, Parolini O, La Rocca G, Deng L. Umbilical cord versus bone marrow-derived mesenchymal stromal cells. Stem Cells Dev. 2012;21:2900–3.

    Article  CAS  PubMed  Google Scholar 

  13. Kavanagh H, Mahon BP. Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy. 2011;66:523–31.

    Article  CAS  PubMed  Google Scholar 

  14. Weiss DJ, Bertoncello I, Borok Z, Kim C, Panoskaltsis-Mortari A, Reynolds S, Rojas M, Stripp B, Warburton D, Prockop DJ. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc. 2011;8:223–72.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cho KS, Roh HJ. Immunomodulatory effects of adipose-derived stem cells in airway allergic diseases. Curr Stem Cell Res Ther. 2010;5:111–5.

    Article  CAS  PubMed  Google Scholar 

  16. Nemeth K, Keane-Myers A, Brown JM, Metcalfe DD, Gorham JD, Bundoc VG, Hodges MG, Jelinek I, Madala S, Karpati S, Mezey E. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci USA. 2010;107:5652–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Park HK, Cho KS, Park HY, Shin DH, Kim YK, Jung JS, Park SK, Roh HJ. Adipose-derived stromal cells inhibit allergic airway inflammation in mice. Stem Cells Dev. 2010;19:1811–8.

    Article  CAS  PubMed  Google Scholar 

  18. Goodwin M, Sueblinvong V, Eisenhauer P, Ziats NP, LeClair L, Poynter ME, Steele C, Rincon M, Weiss DJ. Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice. Stem Cells. 2011;29:1137–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. de Vries JE. The role of IL-13 and its receptor in allergy and inflammatory responses. J Allergy Clin Immunol. 1998;102:165–9.

    Article  PubMed  Google Scholar 

  20. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.

    Article  CAS  PubMed  Google Scholar 

  21. Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther. 2011;2:34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Slater BJ, Kwan MD, Gupta DM, Panetta NJ, Longaker MT. Mesenchymal cells for skeletal tissue engineering. Expert Opin Biol Ther. 2008;8:885–93.

    Article  CAS  PubMed  Google Scholar 

  23. Tyndall A, Uccelli A. Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks. Bone Marrow Transplant. 2009;43:821–8.

    Article  CAS  PubMed  Google Scholar 

  24. Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum. 2010;62:2467–75.

    Article  CAS  PubMed  Google Scholar 

  25. Liu Y, Mu R, Wang S, Long L, Liu X, Li R, Sun J, Guo J, Zhang X, Guo J, Yu P, Li C, Liu X, Huang Z, Wang D, Li H, Gu Z, Liu B, Li Z. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther. 2010;12:R210.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106:1755–61.

    Article  CAS  PubMed  Google Scholar 

  27. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007;109:228–34.

    Article  CAS  PubMed  Google Scholar 

  28. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–22.

    Article  CAS  PubMed  Google Scholar 

  29. Bouffi C, Bony C, Courties G, Jorgensen C, Noel D. IL-6-dependent PGE2 secretion by mesenchymal stem cells inhibits local inflammation in experimental arthritis. PLoS One. 2010;5:e14247.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen K, Wang D, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Zhu D, Bayard F, Han ZC. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol. 2010;135:448–58.

    Article  CAS  PubMed  Google Scholar 

  31. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110:3499–506.

    Article  CAS  PubMed  Google Scholar 

  32. Ozaki K, Sato K, Oh I, Meguro A, Tatara R, Muroi K, Ozawa K. Mechanisms of immunomodulation by mesenchymal stem cells. Int J Hematol. 2007;86:5–7.

    Article  CAS  PubMed  Google Scholar 

  33. Wolf D, Wolf AM. Mesenchymal stem cells as cellular immunosuppressants. Lancet. 2008;371:1553–4.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by grants from the National Science Council, Taiwan (NSC 101-2320-B-182-033) and Chang Gung Memorial Hospital (CMRPD1D0411-3).

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Correspondence to Kang-Hsi Wu or Jing-Long Huang.

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No financial support or other benefits from commercial sources was provided for this work.

Additional information

Responsible Editor: John Di Battista.

C.-K. Chan and T.-C. Lin contributed equally to this work.

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Chan, CK., Lin, TC., Huang, YA. et al. The modulation of Th2 immune pathway in the immunosuppressive effect of human umbilical cord mesenchymal stem cells in a murine asthmatic model. Inflamm. Res. 65, 795–801 (2016). https://doi.org/10.1007/s00011-016-0961-y

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  • DOI: https://doi.org/10.1007/s00011-016-0961-y

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